The primary objective of this project is to investigate the neural architecture of complex vocal communication in a natural mammalian system, Alston's singing mouse (Scotinomys teguina). We focus on the expression and function of Foxp2, a gene implicated in both the evolution of human language and the genesis of human communicative disorders. The remarkably complex vocalizations for which singing mice are named provide a natural behavioral phenotype in which the effects of manipulation of gene expression on the production of acoustic signals can be measured directly. We propose three specific aims. First, we will conduct a series of neuroanatomical studies in which we will, a) quantify differential Foxp2 expression in the striatum using immunocytochemistry and stereology, b) co-localize Foxp2 with cellular markers relevant to striatal motor circuits using fluorescently-labled antibodies, and c) quantify Foxp2 expression in sensory-motor circuits during S. teguina call development. Second, we will use immediate early genes to identify brain regions activated during call production and co-localize Foxp2 expression with immediate early gene induction. Third, we will selectively silence Foxp2 expression in the dorsal striatum of pre-vocal and adult males by injecting Foxp2-shRNA packaged in a recombinant adeno-associated viral vector. The functional consequences of targeted knockdown of Foxp2 will be assessed with a series of simple behavioral assays, designed to discriminate specific deficits in call production and orofacial motor control from general deficits in motor function. To our knowledge, this will be the first targeted manipulation of Foxp2 in a mammal. In combination, the results of this study should make an important contribution to knowledge of the functional neuroanatomy of Foxp2, and understanding of the mechanistic control of complex acoustic communication in a natural mammalian system. Such a model could prove more generally useful in understanding the mechanisms underlying communication disorders. Foxp2 is the first gene implicated in the genesis of human language disorders; its dysfunction produces deficits in perceiving and producing grammatical statements, as well as the ability to make the fine, temporally structured orofacial movements that characterize speech. We propose to explore Foxp2 expression and function in a novel model for mammalian vocal communication, the singing mouse. By doing so, we hope to advance understanding of the contribution of the basal ganglia to communication disorders including verbal dyspraxia, autism and specific language impairment. [unreadable] [unreadable] [unreadable]